Interbody bone implant device

ABSTRACT

An expandable implant device for implantation at a surgical site is provided. The implant device is made of cortical bone and includes a top and bottom piece, both pieces configured to couple with each other. The top piece has superior and inferior surfaces, and at least a tapered leading end configured to distract open an intervertebral disc space so that the top piece can be slidably inserted over the bottom piece until a desired overlap is achieved. A composite interbody bone implant device is also provided including a body skeleton having a non-bone composition, such as a polymer, formed into a shape and including one or more cavities which can be filled with other material, for example, allograft material. A method of placing an expandable device into a disc space is also provided.

BACKGROUND

Chronic back problems cause pain and disability for a large segment ofthe population. In many cases, chronic back problems are caused byintervertebral disc disease. When an intervertebral disc is diseased,the vertebrae between which the disc is positioned may be inadequatelysupported, resulting in persistent pain. Stabilization and/orarthrodesis of the intervertebral joint can reduce the pain anddebilitating effects associated with disc disease.

Spinal stabilization systems and procedures have been developed tostabilize diseased intervertebral joints and, in some cases, to fuse thevertebrae that are adjacent to the diseased joint space. Most fusiontechniques include removing some or all of the disc material from theaffected joint, and stabilizing the joint by inserting an implant, forexample, a bone graft or other material to facilitate fusion of thevertebrae, in the cleaned intervertebral space.

The use of bone grafts and bone substitute materials in orthopedicmedicine is known. Conventionally, bone tissue regeneration is achievedby filling a bone repair site with a bone graft. Over time, the bonegraft is incorporated by the host and new bone remodels the bone graft.In order to place the bone graft, it is common to use a monolithic bonegraft or to form an osteoimplant comprising particulated bone in acarrier. The carrier is thus chosen to be biocompatible, to beresorbable, and to have release characteristics such that the bone graftis accessible. The natural cellular healing and remodeling mechanisms ofthe body coordinate removal of bone and bone grafts by osteoclast cellsand formation of bone by osteoblast cells.

In the spinal surgery field, surgical procedures are often performed tocorrect problems with displaced, damaged or degenerated intervertebraldiscs due to trauma, disease or aging. Bone graft materials are oftenused in spine fusion surgery. Current spinal fusion implants utilizegrafts of either bone or artificial implants to fill the intervertebraldisc space.

In particular, one method of treating a damaged disc is by immobilizingthe area around the injured portion and fusing the immobilized portionby promoting bone growth between the immobilized spine portions. Thisoften requires implantation of an intervertebral device to provide thedesired spacing between adjacent vertebrae to maintain foraminal heightand decompression. That is, an intervertebral implant comprising aninterbody fusion device may be inserted into the intervertebral discspace of two neighboring vertebral bodies or into the space created byremoval of damaged portions of the spine.

In some instances, a formed implant, whether monolithic or particulatedand in a carrier, is substantially solid at the time of implantation andthus does not conform to the implant site. Further, most implants aresubstantially formed at the time of implantation in limited sizes andshapes and provide little ability for customization.

While generally effective, the use of bone grafts has some limitations.Autologous bone grafts, being obtained from the patient, requireadditional surgery and present increased risks associated with itsharvesting, such as risk of infection, blood loss and compromisedstructural integrity at the donor site. Bone grafts using cortical boneremodel slowly because of their limited porosity. Traditional bonesubstitute materials and bone chips are more quickly remodeled butcannot immediately provide mechanical support. In addition, while bonesubstitute materials and bone chips can be used to fill oddly shapedbone defects, such materials are not as well suited for wrapping orresurfacing bone. Indeed, the use of bone grafts is generally limited bythe available shapes and sizes of grafts provided.

With regards to bone grafts, allograft bone is a reasonable bone graftsubstitute for autologous bone. It is readily available from cadaversand avoids the surgical complications and patient morbidity associatedwith harvesting autologous bone. Allograft bone is essentially aload-bearing matrix comprising cross-linked collagen, hydroxyapatite,and osteoinductive bone morphogenetic proteins. Human allograft tissueis widely used in orthopaedic surgery.

Indeed, an allograft implant is a preferred material by surgeons forconducting interbody fusions because it will remodel over time into hostbone within the fusion mass. However, though allograft tissue hascertain advantages over the other treatments, allograft implants aretypically available in limited size ranges, thus making it difficult toprovide implants, in particular, interbody implants in a preferredgeometrical shape. Indeed, allograft implants may only provide temporarysupport, as it is difficult to manufacture the allograft with aconsistent shape and strength. On the other hand, synthetic polymerimplants such as poly-ether-ether-ketone (PEEK) can be manufactured intoany geometrical shape. However, synthetic polymer implants, unlikeallograft implants, have some strength limitations and will not remodelinto host bone over time like an allograft implant. Synthetic polymerimplants also do not allow for direct bone attachment or bonding tofurther stabilize the implant and fusion mass. In addition, surgicalprocedures are increasingly moving towards minimally invasive surgicalprocedures in which smaller interbody cages can be inserted throughsmaller surgical incisions and expanded once placed in the disc space.Because of the allograft size limitations, current expandable interbodycages are generally manufactured from metal and plastic materials.

Therefore, it would be desirable to construct an implant, particularlyan interbody implant, that has components that allow remodeling and discdistraction.

SUMMARY

The present disclosure fills the need by providing devices (for example,medical devices), systems and methods for enhancing the utility ofallograft tissue as an interbody fusion material. In particular, thepresent disclosure provides an expandable implant device forimplantation at a surgical site. The implant device is prepared ofcortical bone and has a top and bottom piece. The bottom piece of theimplant device has superior and inferior surfaces and is configured tocouple with the top piece. The top piece also has superior and inferiorsurfaces, a leading end and a trailing end. The leading end, in someembodiments, of the top piece is tapered or narrower in size and isconfigured to distract open an intervertebral disc space so that the toppiece can be slidably inserted over the bottom piece until a desiredoverlap is achieved.

In another aspect, the superior surface of the bottom piece and theinferior surface of the top piece, each comprise a mechanical featureconfigured to interlock the top piece with the bottom piece. In variousaspects, the mechanical feature comprises a recess, projection, rib,groove or a combination thereof. The superior surface of the bottompiece and the inferior surface of the top piece are configured to slideover one another.

In certain embodiments, the top and bottom pieces of the expandableimplant device can have many shapes including circular, oblong, oval,curved, triangular, other polygonal or non-polygonal shapes. In otherembodiments, the tapered leading end of the top piece has a shape thatis bullet, round, oval, curved or triangular in shape.

In various other embodiments, the present disclosure provides anexpandable implant device comprising a composite of allograft bonetissue and a non-bone composition such as a polymer composition, forexample, poly-ether-ether-ketone (PEEK) and/or other polymercompositions. According to some embodiments, a composite bone implantdevice is provided which utilizes and retains allograft pieces within apolymer structure. This advantageously enables the beneficial propertiesof allograft tissue and the beneficial attributes of polymers to befully realized. For example, the remodeling capability of allografttissue is advantageously combined with the polymer's ability to enableimplants to be formed into any geometrical shape or size.

In some embodiments, the composite implant is configured to increase thesurface area contact of the allograft with the host bone, which willresult in faster fusion and incorporation of the composite implant intohost bone that allows a stronger fusion mass. In some embodiments, theallograft bone used in the implant is surface demineralization toincrease its osteoinductivity and fusion with the host bone. In someembodiments, the implant optimizes the non-bone and bone content of theimplant body such that the majority of the mechanical load is carried bythe allograft, while the non-bone material holds the allograft piecestogether. In some embodiments, the portion of the allograft that is notdemineralized comprises load bearing and/or higher compressive strengthallograft material.

According to one aspect, an implant device is provided comprising abody, which comprises a skeleton of non-bone composition formed into ashape and including at least one cavity. The implant device alsocomprises a biocompatible material provided within the at least onecavity of the body skeleton, wherein the body skeleton is formable intoa shape and size adapted for implantation at a surgical site.

In various embodiments, the implant device having a skeleton body and atleast one cavity therein comprises a top piece and a bottom piece. Thebottom piece of the implant device has superior and inferior surfacesand is configured to couple with the top piece. The top piece hassuperior and inferior surfaces, a leading end and a trailing end. Theleading end of the top piece is tapered or narrower than the trailingend and is configured to distract open an intervertebral disc space sothat the top piece can be slidably inserted over the bottom piece untila desired overlap is achieved. Both the top and bottom pieces areprepared of non-bone material to provide a polymeric skeleton whichcontains at least one cavity. The non-bone composition includes at leastone of a polymer, ceramic, metal or combinations thereof. In severalaspects, the skeleton comprises poly-ether-ether-ketone (PEEK),poly-ether-ketone-ketone (PEKK), or a combination thereof.

In various embodiments, a biocompatible material is provided within theat least one cavity of the bottom piece or the top piece or both. Thebiocompatible material can comprise an osteoinductive material. Theosteoinductive material comprises at least one of autologous bone, boneallograft, bone xenograft or a non-bone implant.

In various embodiments, the superior surface of the bottom piece and theinferior surface of the top piece of the composite implant devicecomprise a mechanical feature configured to interlock the bottom piecewith the top piece. The mechanical feature comprises a recess,projection, rib, groove or a combination thereof.

This disclosure also provides a method of placing an expandable implantdevice into a disc space. The method includes the steps of inserting abottom piece of the implant device into a disc space and holding thebottom piece stationary with an insertion instrument; inserting a toppiece with a ratcheting instrument, the top piece having superior andinferior surfaces, a tapered leading end and a trailing end, the leadingtapered end of the top piece configured to distract open anintervertebral disc space for slidably inserting the top piece over thebottom piece. In some embodiments, the top piece and the bottom piececomprise cortical bone. In other embodiments the top piece and thebottom piece comprise non-bone composition including at least onecavity. In other embodiments, the superior surface of the bottom pieceand the inferior surface of the top piece comprise a mechanical featureconfigured to interlock the top piece over the bottom piece. In severalaspects, the at least one cavity in the top piece, the bottom piece orboth is provided with biocompatible material.

According to another aspect, a composite interbody bone implant deviceis provided comprising a body, which comprises a non-bone compositionformed into a shape and including a plurality of cavities and anosteoinductive material provided within the cavities of the body,wherein the body is formable into a shape and size adapted forimplantation at a surgical site.

While multiple embodiments are disclosed, still other embodiments of thepresent disclosure will become apparent to those skilled in the art fromthe following detailed description, which is to be read in connectionwith the accompanying drawing(s). As will be apparent, the disclosure iscapable of modifications in various obvious aspects, all withoutdeparting from the spirit and scope of the present disclosure.Accordingly, the detailed description is to be regarded as illustrativein nature and not restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

In part, other aspects, features, benefits and advantages of theembodiments will be apparent with regard to the following description,appended claims and accompanying drawing(s) where:

FIG. 1 is a front sectional view of an exemplary expandable bone implantaccording to one embodiment;

FIG. 2 is a top view of a straight shaped expandable implant accordingto another embodiment;

FIG. 3 is top view of an expandable curved shaped bone implant deviceaccording to an alternate embodiment;

FIG. 4 is a front sectional view of an exemplary expandable bone implantdevice according to another embodiment;

FIG. 5 is a cross sectional view through the center of the expandablebone implant illustrated in FIG. 4;

FIG. 6 is a top view of the expandable bone implant illustrated in FIG.4;

FIG. 7 is a side view of another exemplary expandable bone implant inaccordance with principles of this disclosure;

FIG. 8 is a front sectional view of another exemplary expandable boneimplant device in accordance with the principles of this disclosure;

FIG. 9 is a front sectional view of an exemplary expandable bone implantaccording to an another embodiment;

FIG. 10 is a side view of another exemplary expandable bone implant inaccordance with principles of this disclosure; and

FIG. 11 depicts a top view of an exemplary implant device insertedwithin an intervertebral disc space in accordance with principles ofthis disclosure.

DETAILED DESCRIPTION

Definitions

To aid in the understanding of the disclosure, the followingnon-limiting definitions are provided:

“Bioactive agent or bioactive compound,” as used herein, refers to acompound or entity that alters, inhibits, activates, or otherwiseaffects biological or chemical events. For example, bioactive agents mayinclude, but are not limited to, osteogenic or chondrogenic proteins orpeptides, anti-AIDS substances, anti-cancer substances, antibiotics,immunosuppressants, anti-viral substances, enzyme inhibitors, hormones,neurotoxins, opioids, hypnotics, anti-histamines, lubricants,tranquilizers, anti-convulsants, muscle relaxants and anti-Parkinsonsubstances, anti-spasmodics and muscle contractants including channelblockers, miotics and anti-cholinergics, anti-glaucoma compounds,anti-parasite and/or anti-protozoal compounds, modulators ofcell-extracellular matrix interactions including cell growth inhibitorsand antiadhesion molecules, vasodilating agents, inhibitors of DNA, RNAor protein synthesis, anti-hypertensives, analgesics, anti-pyretics,steroidal and non-steroidal anti-inflammatory agents, anti-angiogenicfactors, angiogenic factors, anti-secretory factors, anticoagulantsand/or antithrombotic agents, local anesthetics, ophthalmics,prostaglandins, anti-depressants, anti-psychotic substances,anti-emetics, and imaging agents. In certain embodiments, the bioactiveagent is a drug. In some embodiments, the bioactive agent is a growthfactor, cytokine, extracellular matrix molecule or a fragment orderivative thereof, for example, a cell attachment sequence such as RGD.

“Biocompatible,” as used herein, refers to materials that, uponadministration in vivo, do not induce undesirable long-term effects.

“Bone,” as used herein, refers to bone that is cortical, cancellous orcortico-cancellous of autogenous, allogenic, xenogenic, or transgenicorigin.

“Demineralized,” as used herein, refers to any material generated byremoving mineral material from tissue, for example, bone tissue. Incertain embodiments, the demineralized compositions described hereininclude preparations containing less than 5% calcium and, in someembodiments, less than 1% calcium by weight. Partially demineralizedbone (for example, preparations with greater than 5% calcium by weightbut containing less than 100% of the original starting amount ofcalcium) is also considered within the scope of the disclosure. In someembodiments, demineralized bone has less than 95% of its originalmineral content. Demineralized is intended to encompass such expressionsas “substantially demineralized,” “partially demineralized,” and “fullydemineralized.”

“Demineralized bone matrix” or “DBM” as used herein, refers to anymaterial generated by removing mineral material from bone tissue. Insome embodiments, the DBM compositions as used herein includepreparations containing less than 5% calcium and, in some embodiments,less than 1% calcium by weight. Partially demineralized bone (forexample, preparations with greater than 5% calcium by weight butcontaining less than 100% of the original starting amount of calcium)are also considered within the scope of the disclosure.

“Osteoconductive,” as used herein, refers to the ability of anon-osteoinductive substance to serve as a suitable template orsubstance along which bone may grow.

“Osteogenic,” as used herein, refers to the ability of an agent,material, or implant to enhance or accelerate the growth of new bonetissue by one or more mechanisms such as osteogenesis, osteoconduction,and/or osteoinduction.

“Osteoimplant,” as used herein, refers to any bone-derived implantprepared in accordance with the embodiments of this disclosure andtherefore is intended to include expressions such as bone membrane orbone graft.

“Osteoinductive,” as used herein, refers to the quality of being able torecruit cells from the host that have the potential to stimulate newbone formation. Any material that can induce the formation of ectopicbone in the soft tissue of an animal is considered osteoinductive.

“Superficially demineralized,” as used herein, refers to bone-derivedelements possessing at least about 90 weight percent of their originalinorganic mineral content, the expression “partially demineralized” asused herein refers to bone-derived elements possessing from about 8 toabout 90 weight percent of their original inorganic mineral content andthe expression “fully demineralized” as used herein refers to bonecontaining less than 8% of its original mineral context.

The term “allograft” refers to a graft of tissue obtained from a donorof the same species as, but with a different genetic make-up from, therecipient, as a tissue transplant between two humans.

The term “autologous” refers to being derived or transferred from thesame individual's body, such as for example an autologous bone marrowtransplant.

The term “implantable” as utilized herein refers to a biocompatibledevice retaining potential for successful surgical placement within amammal.

The expression “implantable device” and expressions of like import asutilized herein refers to any object implantable through surgical,injection, or other suitable means whose primary function is achievedeither through its physical presence or mechanical properties.

The term “morbidity” refers to the frequency of the appearance ofcomplications following a surgical procedure or other treatment.

The term “osteoinduction” refers to the ability to stimulate theproliferation and differentiation of pluripotent mesenchymal stem cells(MSCs). In endochondral bone formation, stem cells differentiate intochondroblasts and chondrocytes, laying down a cartilaginous ECM, whichsubsequently calcifies and is remodeled into lamellar bone. Inintramembranous bone formation, the stem cells differentiate directlyinto osteoblasts, which form bone through direct mechanisms.Osteoinduction can be stimulated by osteogenic growth factors, althoughsome ECM proteins can also drive progenitor cells toward the osteogenicphenotype.

The term “osteoconduction” refers to the ability to stimulate theattachment, migration, and distribution of vascular and osteogenic cellswithin the graft material. The physical characteristics that affect thegraft's osteoconductive activity include porosity, pore size, andthree-dimensional architecture. In addition, direct biochemicalinteractions between matrix proteins and cell surface receptors play amajor role in the host's response to the graft material.

The term “osteogenic” refers to the ability of a graft material toproduce bone independently. To have direct osteogenic activity, thegraft must contain cellular components that directly induce boneformation. For example, a collagen matrix seeded with activated MSCswould have the potential to induce bone formation directly, withoutrecruitment and activation of host MSC populations. Because manyosteoconductive scaffolds also have the ability to bind and deliverbioactive molecules, their osteoinductive potential will be greatlyenhanced.

The term “patient” refers to a biological system to which a treatmentcan be administered. A biological system can include, for example, anindividual cell, a set of cells (for example, a cell culture), an organ,or a tissue. Additionally, the term “patient” can refer to animals,including, without limitation, humans.

The term “treating” or “treatment” of a disease refers to executing aprotocol, which may include administering one or more drugs to a patient(human or otherwise), in an effort to alleviate signs or symptoms of thedisease. Alleviation can occur prior to signs or symptoms of the diseaseappearing, as well as after their appearance. Thus, “treating” or“treatment” includes “preventing” or “prevention” of disease. Inaddition, “treating” or “treatment” does not require completealleviation of signs or symptoms, does not require a cure, andspecifically includes protocols, which have only a marginal effect onthe patient.

The term “xenograft” refers to tissue or organs from an individual ofone species transplanted into or grafted onto an organism of anotherspecies, genus, or family.

For the purposes of this specification and appended claims, unlessotherwise indicated, all numbers expressing quantities of ingredients,percentages or proportions of materials, reaction conditions, and othernumerical values used in the specification and claims, are to beunderstood as being modified in all instances by the term “about.”Accordingly, unless indicated to the contrary, the numerical parametersset forth in the following specification and attached claims areapproximations that may vary depending upon the desired propertiessought to be obtained by the present disclosure. At the very least, andnot as an attempt to limit the application of the doctrine ofequivalents to the scope of the claims, each numerical parameter shouldat least be construed in light of the number of reported significantdigits and by applying ordinary rounding techniques.

Certain terminology, which may be used in the following description isfor convenience only and is not limiting. For example, the words“right”, “left”, “top” and “bottom” designate directions in the drawingsto which reference is made. The words, “anterior”, “posterior”,“superior”, “inferior”, “lateral” and related words and/or phrasesdesignate preferred positions and orientations in the human body towhich reference is made and are not meant to be limiting. Theterminology includes the above-listed words, derivatives thereof andwords of similar import.

Expandable Implant Devices

Bone allograft is a preferred material by surgeons for conductinginterbody fusions because it will remodel over time into host bonewithin the fusion mass, but a limitation with the allograft is that itis only available in limited size ranges making it difficult to provideinterbody implants in a preferred geometrical shape. On the other hand,synthetic polymers such as poly-ether-ether-ketone (PEEK) can bemanufactured into any geometrical shape, but have some strengthlimitations and are a permanent implant that will not remodel into hostbone over time like an allograft. Polymer compositions also do not allowfor direct bone attachment or bonding to further stabilize the implantand fusion mass. In addition, surgical procedures are increasinglymoving towards minimally invasive surgical procedures in which smallerinterbody cages can be inserted through smaller surgical incisions andexpanded once placed in the disc space. Because of the allograft sizelimitations, current expandable interbody cages are manufacture frommetal and plastic materials.

The present disclosure overcomes the drawbacks of the prior art byproviding various exemplary designs of bone implants comprisingdesirable remodelable allograft composition and disc distractionproperties. The present disclosure also provides implants containingnon-bone skeleton structures configured to include cavities includingother materials, for example, allograft material.

In some embodiments, the composite implant is configured to increase thesurface area contact of the allograft with the host bone, which willresult in faster fusion and incorporation of the composite implant intohost bone that allows a stronger fusion mass. In some embodiments, theallograft bone used in the implant is surface demineralization toincrease its osteoinductivity and fusion with the host bone. In someembodiments, the implant optimizes the non-bone and bone content of theimplant body such that the majority of the mechanical load is carried bythe allograft, while the non-bone material holds the allograft piecestogether. In some embodiments, the portion of the allograft that is notdemineralized comprises load bearing and/or higher compressive strengthallograft material.

Various exemplary configurations according to the present disclosureinvolve providing cortical allograft constructs that mechanicallyinterlock together and slide over each other to distract open theintervertebral disc space as they are inserted to form a singleinterbody implant. Advantageously, it is noted that an implant devicemay be provided in any configuration, size and shape, as per therequirements of the desired target site. Thus, almost unlimited rangesof sizes and shapes of optimized bone implant devices may be provided.In one example, an implant device may be configured to be adapted foruse as an interbody fusion device, for example, in spinal fusionprocedures. However, alternate configurations of the implant device maybe contemplated to suit the needs of a patient's bone graft target site.

FIG. 1 depicts a representative expandable bone implant 100 preparedfrom cortical allograft. Implant 100 comprises, consists essentially ofor consists of two elements, a top piece 102 and a bottom piece 104.Each piece has a superior and an inferior surface. Accordingly, toppiece 102 has a superior surface 108 and an inferior surface 110.Similarly, the bottom piece 104 has a superior surface 112 and aninferior surface 114. Each superior and inferior surfaces are joined bysurfaces forming a leading end and a trailing end. Accordingly, toppiece 102 has a leading end 116 and a trailing end 118 and bottom piece104 has a leading end 120 and a trailing end 122. The bottom allograftpiece 104 has a mechanical feature (not shown in FIG. 1), for example arib, groove, recess, and/or projection that can interlock with the topallograft piece 102.

The bottom allograft piece 104 can be inserted first in disc space 106.Leading end 116 of top allograft piece 102 is tapered or narrower thantrailing end 118 so that top piece 102 can distract open disc space 106and slide over the bottom allograft piece 104 until the two pieces lockinto place. An insertion tool can be used to hold the bottom piece 104in place as the top piece 102 is pushed slidingly over bottom piece 104utilizing, for example, a ratcheting mechanism. The inferior surface ofthe top piece slidably engages the superior surface of the bottom piece.One or more surfaces of the top and/or bottom piece may comprise alubricant to reduce friction and ease insertion.

In some embodiments, the implant device contacts host bone and theimplant device comprises non-bone material, the contact surface area ofthe non-bone material and the cortical bone to the host bone comprisesfrom about 5% to about 50% or from about 10% to about 20% of theimplant. In some embodiments, the implant device comprises non-bonematerial and the non-bone material comprises from about 10 wt. % toabout 60 wt. % of the implant. In some embodiments, the implant devicecomprises bone material and the bone material comprises from about 40wt. % to about 90 wt. % of the implant. In some embodiments, the implantdevice comprises bone material and the bone material comprises fromabout 10 wt. % to about 60 wt. % of the implant.

FIG. 2 illustrates another embodiment of the expandable bone implant 200having a straight shape, while FIG. 3 illustrates another embodimentwherein the expandable bone implant 300 has a curved shape dependingupon the desired form best suited for a selected surgical procedure.Bone implant device 200 comprises a top piece 202 and a bottom piece 204configured to lock one on top of the other. Similarly, bone implantdevice 300 comprises a top piece 302 and a bottom piece 304 configuredto lock one on top of the other. The implant is expandable as the bottompiece is expanded by the depth, width and height of the top piece. Insome embodiments, the polymer and/or allograft material will also expandas it contacts bodily fluid after implantation at the target tissuesite.

FIG. 4 illustrates a front sectional view of another embodiment of anexpandable bone implant 400 prepared from cortical allograft andcomprising, consisting essentially of or consisting of two elements, atop piece 402 and a bottom piece 404. Top piece 402 has leading end 406and trailing end 408, the leading end 406 is tapered in a bullet noseconfiguration as shown in FIG. 5.

FIG. 5 is a cross section view of the implant device 500 taken throughthe center of the implant device shown in FIG. 4. Top piece 502 has asuperior surface 506 and an inferior surface 508, a leading end 510 anda trailing end 512. Leading end 510 has the tapered configuration of abullet nose enabling top piece 502 to distract open disc space 514 toslide over the bottom piece 504 until the two pieces lock into place.

FIG. 6 is a top view of an expandable bone implant 600 as illustrated inFIG. 4. In yet another embodiment illustrated in FIG. 7, expandable boneimplant 700 comprises, consists essentially of or consists of a toppiece 702 and a bottom piece 704, both manufactured from corticalallograft. Top piece 702 has superior and inferior surfaces 706 and 708and bottom piece 704 has superior and inferior surfaces 710 and 712.Inferior surface 708 of top piece 702 includes at least one projectionor rib 714 while superior surface 710 of bottom piece 704 has a recessor groove 716. Projection or rib 714 locks with recess or groove 716 astop piece 702 slides over bottom piece 704 with the help of, in someembodiments, a ratcheting inserter. The recess and/or projection, insome embodiments, can be mating and include, for example, correspondingvoids, apertures, bores, depressions, holes, indentations, grooves,channels, notches or the like, which can mate with each other. Like toppiece 502 illustrated in FIG. 5, top piece 702 has a tapered leading end718 enabling top piece 702 to distract the disc space open beforesliding over the bottom piece 704 until projection 714 locks into recess716.

FIG. 8 is a front sectional view of yet another embodiment of theexpandable allograft bone implant 800 having a top piece 802 that istriangularly shaped to mate with a bottom piece 804.

FIG. 9 illustrates a front sectional view of another embodiment of anexpandable implant device 900. In this embodiment, both the top piece902 and the bottom piece 904 comprise a polymer skeleton 906, forexample, PEEK, and at least one cavity 908 that can be packed withcortical allograft inserts. Advantageously, the incorporation of PEEKskeletons for the top and bottom pieces of the expandable implant allowsfor the incorporation of design features that enable a better mechanicallock of the top and bottom pieces and adaptation to insertioninstruments.

FIG. 10 is a side view of another embodiment of an expandable implant1000 wherein the top and bottom pieces 1002, 1004 have a polymerskeleton 1006 having two cavities 1008, 1010 that can be filled withallograft as indicated in phantom by interrupted lines.

FIG. 11 is a top view of an expandable implant 1100 according to oneembodiment. Implant 1100 may comprise a body skeleton 1102 which maycomprise, a ‘skeleton’ structure configured to include at least onewindow or cavity within which a substance 1108, such as an allograftmaterial may be inserted and retained. The term ‘cavity’ includes andencompasses voids, apertures, bores, depressions, holes, indentations,grooves, channels, notches or the like. In some embodiments the skeletoncomprises a plurality of cavities. As illustrated in FIG. 11, bodyskeleton 1102 includes two cavities 1104, 1106 which may be providedthroughout one or more surfaces of and/or within the body skeleton 1102,thus enabling a plurality of allograft pieces to be retained by the body1102 in various locations.

The body 1102 may comprise any non-bone composition, in particular, anybiocompatible material including but not limited to a metal, such as,for example, cobalt-chromium-molybdenum (CCM) alloys, titanium, titaniumalloys, stainless steel, aluminum, a ceramic such as, for example,zirconium oxide, silicon nitride, an allograft, an autograft, ametal-allograft composite, a polymer such as, for example, polyarylether ketone (PAEK), polyether ether ketone (PEEK), polyether ketoneketone (PEKK), polyetherketone (PEK), polyetherketoneether-ketone-ketone (PEK-EKK) or a combination thereof. The polymers maybe reinforced with a fiber such as, for example, a carbon fiber or otherthin, stiff fiber.

Advantageously, the body 1102 may be formed, for example, via injectionmolding and/or machining into any size or shape to accommodate thedesired application and/or delivery conditions. The body 1102 mayfurther be configured to include any desired features, such as cavities,projections, in any desired location or orientation, as discussedfurther below.

In various embodiments, the delivery of the expandable implant deviceand its component pieces can be facilitated by using a lubricant tolubricate the implant device and its components prior to insertion intoan intervertebral disc space. Suitable lubricants include withoutlimitation mineral oils, bodily fluids, fat, saline or hydrogelcoatings. Other useful lubricants include hyaluronic acid, hyaluronan,lubricin, polyethylene glycol and combinations thereof.

The body of all expandable implants according to principles of thisdisclosure may also include a mechanism or feature for engaging animplant insertion instrument. The mechanism or feature for engaging theinsertion instrument may take on any form including, for example, one ormore bores for receiving one or more projections formed on the implantinsertion instrument, one or more projections for engaging one or morebores formed on the implant insertion instrument, one or more channelsfor receiving one or more tips formed on the implant insertioninstrument, one or more threaded bores for receiving one or morethreaded shafts or screws.

The body of the expandable implants described herein may also include amechanism or features for reducing and/or preventing slippage ormigration of the implant device 1100 during insertion. For example, oneor more surfaces of the body 1102 may include projections such as ridgesor teeth for increasing the friction between the device 1100 and theadjacent contacting surfaces of the vertebral bodies so to preventmovement of the implant device 1100 after introduction to a desired discspace.

In some embodiments, the surfaces of the body 1102 include at least onecavity 1104 or a plurality of cavities 1104, 1106. Each cavity 1104,1106 may be provided in any of a variety of shapes in addition to thegenerally rectangular shape shown in FIG. 11, including but not limitedto generally circular, oblong, curved, triangular and other polygonal ornon-polygonal shapes. The same or different types of cavity shapes andsizes may be provided in each body 1102. Each cavity 1104, 1106 may beformed to pass entirely through the body 1102 for promoting fusionbetween the upper and lower vertebral bodies so as to allow a boneybridge to form through the implant device 1100. Alternately, cavities1104, 1106 may be formed to partially pass through the body 1102, or maybe formed only on one or more surfaces thereof.

In addition to the body of the expandable implant being enabled to beprovided in various configurations, shapes and sizes, the body mayinclude any number of cavities in different arrangements, locations,sizes and shapes. For example, the arrangement and location of cavitiesmay be determined based on application of the implant device.

According to some embodiments, fusion may be facilitated or augmented byintroducing or positioning various osteoinductive and/or osteogenicmaterials within the cavities in the implant device. Such osteoinductivematerials may be introduced before, during, or after insertion of theexemplary implant device, and may include (but are not necessarilylimited to) autologous bone harvested from the patient receiving theimplant device, bone allograft, bone xenograft, any number of non-boneimplants (for example ceramic, metallic, polymer), bone morphogenicprotein, and/or bio-resorbable compositions. The osteogenic material maybe selected from among many known to those skilled in the art. Forexample, the osteogenic material may comprise minerals such as calciumphosphate or calcium sulfate minerals, bone, including xenograft,allograft or autograft bone, or the like. The osteogenic material mayalso comprise demineralized bone matrix (DBM), osteoinductive factorssuch as bone morphogenetic proteins (for example human BMP-2 or humanBMP-7 or heterodimers thereof) whether recombinantly produced orpurified from tissues, LIM mineralization proteins (LMPs), or the like.The osteogenic material may also comprise a binder material such asblood, clottable blood fractions, platelet gel, collagen, gelatin,carboxymethyl cellulose, or other similar materials that will serve tobind together harder particles or materials such as mineral particles(for example bone or synthetic mineral particles) so as to create athree-dimensionally stable mass when compacted into the cavities of theimplant device.

In some embodiments, the composite interbody bone implant may comprisean allograft portion that is configured to be joined to anotherallograft portion or a non-allograft portion comprising a polymer. Inthis way, the composite interbody device can be joined before it isimplanted at or near the target site. The composite interbody implantcan have mating surfaces comprising recesses and/or projections andreciprocating recesses and/or projections (for example, joints) thatallow the implant to be assembled before implantation. Assembly can alsoinclude, for example, use of an adhesive material to join parts of theimplant together and provide strong interlocking fit.

The adhesive material may comprise polymers having hydroxyl, carboxyl,and/or amine groups. In some embodiments, polymers having hydroxylgroups include synthetic polysaccharides, such as for example, cellulosederivatives, such as cellulose ethers (for example,hydroxypropylcellulose). In some embodiments, the synthetic polymershaving a carboxyl group, may comprise poly(acrylic acid),poly(methacrylic acid), poly(vinyl pyrrolidone acrylicacid-N-hydroxysuccinimide), and poly(vinyl pyrrolidone-acrylicacid-acrylic acid-N-hydroxysuccinimide) terpolymer. For example,poly(acrylic acid) with a molecular weight greater than 250,000 or500,000 may exhibit particularly good adhesive performance. In someembodiments, the adhesive can be a polymer having a molecular weight ofabout 2,000 to about 5,000, or about 10,000 to about 20,000 or about30,000 to about 40,000.

In some embodiments, the adhesive can comprise imido ester,p-nitrophenyl carbonate, N-hydroxysuccinimide ester, epoxide,isocyanate, acrylate, vinyl sulfone, orthopyridyl-disulfide, maleimide,aldehyde, iodoacetamide or a combination thereof. In some embodiments,the adhesive material can comprise at least one of fibrin, acyanoacrylate (for example, N-butyl-2-cyanoacrylate,2-octyl-cyanoacrylate), a collagen-based component, a glutaraldehydeglue, a hydrogel, gelatin, an albumin solder, and/or a chitosanadhesives. In some embodiments, the hydrogel comprises acetoacetateesters crosslinked with amino groups or polyethers as mentioned in U.S.Pat. No. 4,708,821. In some embodiments, the adhesive material cancomprise poly(hydroxylic) compounds derivatized with acetoacetate groupsand/or polyamino compounds derivatized with acetoacetamide groups bythemselves or the combination of these compounds crosslinked with anamino-functional crosslinking compounds.

The adhesive can be a solvent based adhesive, a polymer dispersionadhesive, a contact adhesive, a pressure sensitive adhesive, a reactiveadhesive, such as for example multi-part adhesives, one part adhesives,heat curing adhesives, moisture curing adhesives, or a combinationthereof or the like. The adhesive can be natural or synthetic or acombination thereof.

Contact adhesives are used in strong bonds with high shear-resistance.Pressure sensitive adhesives form a bond by the application of lightpressure to bind the adhesive with the target tissue site, cannulaand/or expandable member. In some embodiments, to have the device adhereto the target tissue site, pressure is applied in a directionsubstantially perpendicular to a surgical incision.

Multi-component adhesives harden by mixing two or more components, whichchemically react. This reaction causes polymers to cross-link intoacrylics, urethanes, and/or epoxies. There are several commercialcombinations of multi-component adhesives in use in industry. Some ofthese combinations are: polyester resin-polyurethane resin;polyols-polyurethane resin, acrylic polymers-polyurethane resins or thelike. The multi-component resins can be either solvent-based orsolvent-less. In some embodiments, the solvents present in the adhesivesare a medium for the polyester or the polyurethane resin. Then thesolvent is dried during the curing process.

In some embodiments, the adhesive can be a one-part adhesive. One-partadhesives harden via a chemical reaction with an external energy source,such as radiation, heat, and moisture. Ultraviolet (UV) light curingadhesives, also known as light curing materials (LCM), have becomepopular within the manufacturing sector due to their rapid curing timeand strong bond strength. Light curing adhesives are generally acrylicbased. The adhesive can be a heat-curing adhesive, where when heat isapplied (for example, body heat), the components react and cross-link.This type of adhesive includes epoxies, urethanes, and/or polyimides.The adhesive can be a moisture curing adhesive that cures when it reactswith moisture present (for example, bodily fluid) on the substratesurface or in the air. This type of adhesive includes cyanoacrylates orurethanes. The adhesive can have natural components, such as forexample, vegetable matter, starch (dextrin), natural resins or fromanimals for example casein or animal glue. The adhesive can havesynthetic components based on elastomers, thermoplastics, emulsions,and/or thermosets including epoxy, polyurethane, cyanoacrylate, oracrylic polymers.

In some embodiments, the interbody bone implant may be joined togetherutilizing pins, rods, clips, or other fasteners to allow strong andeasily coupling of component parts. In some embodiments, the allograftmaterial is configured to provide the most contact to tissue surfaces(for example, the allograft material can be on the perimeter of thedevice, while the polymer material is situated in the interior of thedevice.

In one embodiment, the osteoinductive material comprises allografttissue. Non-limiting examples of a bone graft material includedemineralized bone matrix, or a bone composite. While allograft bone isa desirable alternative to autograft, it must be rigorously processedand terminally sterilized prior to implantation to remove the risk ofdisease transmission or an immunological response. This processingremoves the osteogenic and osteoinductive properties of the allograft,leaving only an osteoconductive scaffold. These scaffolds are availablein a range of preparations (such as morselized particles and struts) fordifferent orthopedic applications.

In one embodiment, to improve the osteoinductive properties, it isdesirable to use demineralized bone matrix (DBM) as the osteoinductivematerial, due to its superior biological properties relative toundemineralised allograft bone, since the removal of minerals increasesthe osteoinductivity of the graft. Currently, there are a range of DBMproducts in clinical use.

Demineralized bone matrix (DBM) is demineralized allograft bone havingosteoinductive activity. DBM is prepared by acid extraction of allograftbone, resulting in loss of most of the mineralized component butretention of collagen and noncollagenous proteins, including growthfactors. DBM does not contain osteoprogenitor cells, but the efficacy ofa demineralized bone matrix as a bone-graft substitute or extender maybe influenced by a number of factors, including the sterilizationprocess, the carrier, the total amount of bone morphogenetic protein(BMP) present, and the ratios of the different BMPs present. DBMincludes demineralized pieces of cortical bone to expose theosteoinductive proteins contained in the matrix. These activateddemineralized bone particles are usually added to a substrate or carrier(for example glycerol or a polymer). DBM is mostly an osteoinductiveproduct, but lacks enough induction to be used on its own in challenginghealing environments such as posterolateral spine fusion.

According to some embodiments of the disclosure, the demineralized bonematrix may comprise demineralized bone matrix fibers and/ordemineralized bone matrix chips. In some embodiments, the demineralizedbone matrix may comprise demineralized bone matrix fibers anddemineralized bone matrix chips in a 30:60 ratio. In some embodiments,the bone allograft material comprises demineralized bone matrix fibersand demineralized bone matrix chips in a ratio of 25:75 to about 75:25fibers to chips.

According to one embodiment of the disclosure, the bone compositecomprises a bone powder, a polymer and a demineralized bone. Indifferent embodiments of the disclosure, bone powder content can rangefrom about 5% to about 90% w/w, polymer content can range from about 5%to about 90% w/w, and demineralized bone particles content comprises thereminder of the composition. In various embodiments, the demineralizedbone particles comprise from about 20% to about 40% w/w while thepolymer and the bone powder comprise each from about 20% to about 60%w/w of the composition. The bone graft materials of the presentdisclosure include those structures that have been modified in such away that the original chemical forces naturally present have beenaltered to attract and bind molecules, including, without limitation,growth factors and/or cells, including cultured cells.

Namely, the demineralized allograft bone material may be furthermodified such that the original chemical forces naturally present havebeen altered to attract and bind growth factors, other proteins andcells affecting osteogenesis, osteoconduction and osteoinduction. Forexample, a demineralized allograft bone material may be modified toprovide an ionic gradient to produce a modified demineralized allograftbone material, such that implanting the modified demineralized allograftbone material results in enhanced ingrowth of host bone.

In one embodiment an ionic force change agent may be applied to modifythe demineralized allograft bone material. The demineralized allograftbone material may comprise, for example, a demineralized bone matrix(DBM) comprising fibers, particles and any combination of thereof.According to another embodiment, a bone graft structure may be usedwhich comprises a composite bone, which includes a bone powder, apolymer and a demineralized bone.

The ionic force change agent may be applied to the entire demineralizedallograft bone material or to selected portions/surfaces thereof. Theionic force change agent may be a binding agent, which modifies thedemineralized allograft bone material or bone graft structure to bindmolecules, such as, for example, growth factors, or cells, such as, forexample, cultured cells, or a combination of molecules and cells. In thepractice of the disclosure the growth factors include but are notlimited to BMP-2, rhBMP-2, BMP-4, rhBMP-4, BMP-6, rhBMP-6, BMP-7(OP-1),rhBMP-7, GDF-5, LIM mineralization protein, platelet derived growthfactor (PDGF), transforming growth factor-β (TGF-β), insulin-relatedgrowth factor-I (IGF-I), insulin-related growth factor-II (IGF-II),fibroblast growth factor (FGF), beta-2-microglobulin (BDGF II), andrhGDF-5. A person of ordinary skill in the art will appreciate that thedisclosure is not limited to growth factors only. Other molecules canalso be employed in the disclosure. For example, tartrate-resistant acidphosphatase, which is not a growth factor, may also be used in thedisclosure.

If a cell culture is employed, the cells include but are not limited tomesenchymal stems cells, pluripotent stem cells, osteoprogenitor cells,osteoblasts, osteoclasts, and any bone marrow-derived cell lines.

In some embodiments, the ionic force change agent comprises at least oneof enzymes, enzyme mixtures, pressure (for example, isostatic pressure),chemicals, heat, sheer force, oxygen plasma, or a combination thereof.For example, the ionic force change agent may comprise an enzyme such ascollagenase or pepsin, which can be administered for a sufficient periodof time to partially digest at least a portion of the demineralizedallograft bone material. Subsequently, the enzyme may be deactivatedand/or removed.

Any enzyme or enzyme mixture may be contemplated, and treatment timedurations may be altered in accordance with the enzyme(s) used. Somesuitable enzymes that may degrade the DBM material include, but are notlimited to, cysteine proteinases, matrix metalloproteinases, enzymessuch as amylases, proteases, lipases, pectinases, cellulases,hemicellulases, pentosanases, xylanases, phytases or combinationsthereof. Exemplary enzymes suitable to partially degrade and modify theDBM material, include but are not limited to, cathepsin L, cathepsin K,cathepsin B, collagenase, pepsin, plasminogen, elastase, stromelysin,plasminogen activators, or a combination thereof.

In some embodiments, the DBM material can be subjected to pressure tomodify it. The simplest pressing technique is to apply pressure to theunconstrained DBM material. Examples include pressing the DBM materialusing a mortar and pestle, applying a rolling/pressing motion such as isgenerated by a rolling pin, or pressing the bone pieces between flat orcurved plates. These flattening pressures cause the DBM material fibersto remain intact.

Another pressing technique involves mechanically pressing demineralizedbone material, which can be constrained within a sealed chamber having ahole (or a small number of holes) in its floor or bottom plate. Theseparated fibers extrude through the holes with the hole diameterlimiting the maximum diameter of the extruded fibers. This constrainedtechnique results in fibers that are largely intact (as far as length isconcerned).

In a combined unconstrained/constrained pressing technique that resultsin longer fibers by minimizing fiber breakage, the demineralized bone isfirst pressed into an initially separated mass of fibers while in theunconstrained condition and thereafter these fibers are constrainedwithin the sealed chamber where pressing is continued.

In general, pressing of demineralized bone to provide demineralized boneparticles can be carried out at from about 1,000 to about 40,000 psi,and, in certain embodiments, at from about 5,000 to about 20,000 psi.

Subsequent to the addition of the ionic force change agent, thepractitioner may optionally administer an appropriate molecule or cellculture. Generally, the molecule or cell culture is applied withinminutes, for example from about 1 to about 120 minutes beforeimplantation into the patient.

One class of molecules suitable for one embodiment of the disclosure isgrowth factors. Growth factors suitable for use in the practice of thedisclosure include but are not limited to bone morphogenic proteins, forexample, BMP-2, rhBMP-2, BMP-4, rhBMP-4, BMP-6, rhBMP-6, BMP-7 (OP-1),rhBMP-7, GDF-5, and rhGDF-5. Bone morphogenic proteins have been shownto be excellent at growing bone and there are several products beingtested. For example, rhBMP-2 delivered on an absorbable collagen sponge(INFUSE® Bone Graft, Medtronic Sofamor Danek, Memphis, Tenn.) has beenused inside titanium fusion cages and resulted in successful fusion andcan be used on a ceramic carrier to enhance bone growth in aposterolateral fusion procedure. rhBMP-2 can also be used on a carrierfor acute, open fractures of the tibial shaft. BMP-7 (OP-1) alsoenhances bone growth in a posterolateral fusion procedure.

Additionally, suitable growth factors include, without limitation, LIMmineralization protein, platelet derived growth factor (PDGF),transforming growth factor β (TGF-β), insulin-related growth factor-I(IGF-I), insulin-related growth factor-II (IGF-II), fibroblast growthfactor (FGF), and beta-2-microglobulin (BDGF II).

Further, molecules, which do not have growth factor properties may alsobe suitable for this disclosure. An example of such molecules istartrate-resistant acid phosphatase.

In one embodiment, the demineralized allograft bone material is treatedwith a negatively-charged ionic force change agent to produce anegatively-charged demineralized allograft bone material. Thenegatively-charged demineralized allograft bone material attracts apositively charged molecule having a pI from about 8 to about 10.Examples of positively charged molecules having a pI from about 8 toabout 10 include but are not limited to, rhBMP-2 and rhBMP-6.

In another embodiment, the demineralized allograft bone material istreated with a positively-charged ionic force change agent such that thepositively-charged demineralized allograft bone material attracts amolecule with a slightly negative charge, for example a charge of pIabout 5 to about 7. Examples of molecules having a slightly negativecharge include rhBMP-4.

In yet another embodiment, the demineralized allograft bone material istreated with a positively-charged ionic force change agent to produce apositively-charged demineralized allograft bone material such thatcells, in particular cell cultures having a negative surface charge bindto the positively-charged demineralized allograft bone material.Examples of cells which are suitable for use in the practice of thedisclosure include but are not limited to mesenchymal stems cells,pluripotent stem cells, embryonic stem cells, osteoprogenitor cells andosteoblasts.

The mechanisms by which a demineralized allograft bone material mayacquire ionic forces include but are not limited to ionization, ionadsorption and ion dissolution. In one embodiment, the implant ismodified to give it the selected charge by a one-to-one substitution ofthe calcium ion with lithium, sodium, potassium or cesium ofhydroxyapatite.

In yet another aspect, treatments with gradient-affecting elements, suchas elements present in hydroxyapatite, and human proteins are employed.Suitable gradient-affecting proteins are those present in the organicphase of human bone tissue. The gradient-affecting proteins derivemolecule or cell attraction without the potential damaging effects onthe implants, as may be the case with other chemical treatments. Usuallythis is accomplished through surface treatments such as, for example,plasma treatment to apply an electrostatic charge on bone.

The term “plasma” in this context is an ionized gas containing excitedspecies such as ions, radicals, electrons and photons. The term “plasmatreatment” refers to a protocol in which a surface is modified using aplasma generated from process gases including, but not limited to, O₂,He, N₂, Ar and N₂O. To excite the plasma, energy is applied to thesystem through electrodes. This power may be alternating current (AC),direct current (DC), radiofrequency (RF), or microwave frequency (MW).The plasma may be generated in a vacuum or at atmospheric pressure. Theplasma can also be used to deposit polymeric, ceramic or metallic thinfilms onto surfaces. Plasma treatment is an effective method touniformly alter the surface properties of substrates having different orunique size, shape and geometry including but not limited to bone andbone composite materials.

In some embodiments, the implant device of the present disclosure havingosteoinductive material retained therein may be used to providetemporary or permanent fixation along an orthopedic target site. Forexample, the expandable implant device may be introduced into anintervertebral disc space while secured to a surgical insertioninstrument and thereafter manipulated into the proper orientation beforebeing released. According to one aspect, the implant device may beintroduced into a target site through use of any of a variety ofsuitable surgical instruments having the capability to engage theimplant device. For example, a clinician may utilize the implant in aminimally invasive spinal fusion procedure. After creation of a workingchannel and preparation of the disc space, a single implant device maybe grasped and placed into the intervertebral disc space. Additionalmaterials and tools may be included in the procedure before, during, orafter the insertion of the implant to aid in introducing the implantinto a targeted spinal site.

In some embodiments, the substance may be designed to expand in vivo.Such an embodiment may be used to fill a space and create contact withcongruent surfaces as it expands in vivo, for example for interbodyfusion. Thus, in some embodiments, the implant device may be used in thedisc space, between implants, or inside a cage.

In some embodiments, the implant devices described in this disclosurecan expand when they come in contact with water or other bodily fluids,either by way of liquid absorption, or by stretching the componentmaterials of these implant devices. As described above, the substancesfrom which the implant devices are made can include a natural and/orsynthetic expandable material. For example, when the implant devices aremade from allograft, then the allograft expands when it comes intocontact with bodily fluids. Similarly, when the implant devices includea polymer skeleton having cavities, the cavities can be filled withexpandable material which results in expanding the implant devices whenthey come into contact with bodily fluids. As described above,expandable material useful to fill up skeleton cavities can comprisebone particles, a polymer, a hydrogel, a sponge, collagen, or othermaterial. In various embodiments, the expandable material comprises boneallograft comprising demineralized bone particles, and the demineralizedbone particles may be a blend of cortical and cancellous bone. Forexample, the expandable material can comprise demineralized corticalfibers and demineralized cancellous chips, wherein the demineralizedcancellous chips can create a matrix for the incorporation of new boneand add advanced expansion characteristics.

In addition to bone particles, an expandable polymer, a collagen sponge,compressed and/or dried hydrogels, or other materials may be used. Inaddition to expansion properties, the material may exhibitosteoinductive and/or osteoconductive properties. For example,cancellous bone particles may exhibit osteoconductive properties whiledemineralized cortical bone particles may exhibit osteoinductiveproperties.

The expandable material may be compressed during formation to aid insubsequent expansion. Generally, increased compression leads toincreased expansion characteristics in the osteoimplant. Compressedmaterials and certain non-compressed materials may be constrained suchthat, absent the constraint, the material is free to expand. Aconstrained material is one that embodies energy, such as a bent,spring-loaded, or coiled material, or any other material that isartificially prevented from expanding or conforming to its naturalconfiguration. The expandable material can be included as filler inskeleton cavities that partially or wholly surround the material.

Expansion may be activated in any suitable manner. For example,expansion may be activated by exposure of the implant device to air,water, blood, heat, removal of a constraint, or otherwise. In oneembodiment, the expandable material may be provided compressed anddried. Upon exposure to liquid in vivo, the expandable material mayexpand. In another embodiment, the expandable may be compressed in theskeleton cavities or at least partially constrained in the skeletoncavities. Upon exposure to liquid in vivo, the cavity filling materialmay expand or disintegrate, as the expandable material expands. Theexpandable material may expand as a function of time. In yet anotherembodiment, the expandable material may have a first state atapproximately 60° F. and an expanded state at approximately 98° F. suchthat, upon implantation in vivo and exposure to body heat, theexpandable material may expand. In a further embodiment, the expandablematerial may be vacuum-sealed during manufacture and, when unsealed andexposed to air, the expandable material may expand.

Having been deposited in the disc space, an implant device of thepresent disclosure effects spinal fusion over time as the naturalhealing process integrates and binds the implant within theintervertebral space by allowing a boney bridge to form through theimplant and between the adjacent vertebral bodies.

In some embodiments, an implant device of the present disclosure may beused to deliver substances such as surface demineralized bone chips,optionally of a predetermined particle size, demineralized bone fibers,optionally pressed, and/or allograft.

For embodiments where the substance is biologic, the substance may beautogenic, allogenic, xenogenic, or transgenic. However, it iscontemplated that other suitable materials may be positioned in theimplant device such as, for example, protein, nucleic acid,carbohydrate, lipids, collagen, allograft bone, autograft bone,cartilage stimulating substances, allograft cartilage, TCP,hydroxyapatite, calcium sulfate, polymer, nanofibrous polymers, growthfactors, carriers for growth factors, growth factor extracts of tissues,demineralized bone matrix, dentine, bone marrow aspirate, bone marrowaspirate combined with various osteoinductive or osteoconductivecarriers, concentrates of lipid derived or marrow derived adult stemcells, umbilical cord derived stem cells, adult or embryonic stem cellscombined with various osteoinductive or osteoconductive carriers,transfected cell lines, bone forming cells derived from periosteum,combinations of bone stimulating and cartilage stimulating materials,committed or partially committed cells from the osteogenic orchondrogenic lineage, or combinations of any of the above. In someembodiments, the substance may be pressed before placement in theimplant device. A substance provided within the implant device may behomogenous, or generally a single substance, or may be heterogeneous, ora mixture of substances.

In some embodiments the substance delivered by the implant device mayinclude or comprise an additive such as an angiogenesis promotingmaterial or a bioactive agent. It will be appreciated that the amount ofadditive used may vary depending upon the type of additive, the specificactivity of the particular additive preparation employed, and theintended use of the composition. The desired amount is readilydeterminable by one skilled in the art. Angiogenesis may be an importantcontributing factor for the replacement of new bone and cartilagetissues. In certain embodiments, angiogenesis is promoted so that bloodvessels are formed at an implant site to allow efficient transport ofoxygen and other nutrients and growth factors to the developing bone orcartilage tissue. Thus, angiogenesis promoting factors may be added tothe substance to increase angiogenesis. For example, class 3semaphorins, for example, SEMA3, controls vascular morphogenesis byinhibiting integrin function in the vascular system, and may be includedin the recovered hydroxyapatite.

In accordance with some embodiments, the substance may be supplemented,further treated, or chemically modified with one or more bioactiveagents or bioactive compounds. Bioactive agent or bioactive compound, asused herein, refers to a compound or entity that alters, inhibits,activates, or otherwise affects biological or chemical events. Forexample, bioactive agents may include, but are not limited to,osteogenic or chondrogenic proteins or peptides; demineralized bonepowder; collagen, insoluble collagen derivatives, and soluble solidsand/or liquids dissolved therein; anti-AIDS substances; anti-cancersubstances; antimicrobials and/or antibiotics such as erythromycin,bacitracin, neomycin, penicillin, polymycin B, tetracyclines, biomycin,chloromycetin, and streptomycins, cefazolin, ampicillin, azactam,tobramycin, clindamycin and gentamycin; immunosuppressants; anti-viralsubstances such as substances effective against hepatitis; enzymeinhibitors; hormones; neurotoxins; opioids; hypnotics; anti-histamines;lubricants; tranquilizers; anti-convulsants; muscle relaxants andanti-Parkinson substances; anti-spasmodics and muscle contractantsincluding channel blockers; miotics and anti-cholinergics; anti-glaucomacompounds; anti-parasite and/or anti-protozoal compounds; modulators ofcell-extracellular matrix interactions including cell growth inhibitorsand antiadhesion molecules; vasodilating agents; inhibitors of DNA, RNA,or protein synthesis; anti-hypertensives; analgesics; anti-pyretics;steroidal and non-steroidal anti-inflammatory agents; anti-angiogenicfactors; angiogenic factors and polymeric carriers containing suchfactors; anti-secretory factors; anticoagulants and/or antithromboticagents; local anesthetics; ophthalmics; prostaglandins;anti-depressants; anti-psychotic substances; anti-emetics; imagingagents; biocidal/biostatic sugars such as dextran, glucose; amino acids;peptides; vitamins; inorganic elements; co-factors for proteinsynthesis; endocrine tissue or tissue fragments; synthesizers; enzymessuch as alkaline phosphatase, collagenase, peptidases, oxidases; polymercell scaffolds with parenchymal cells; collagen lattices; antigenicagents; cytoskeletal agents; cartilage fragments; living cells such aschondrocytes, bone marrow cells, mesenchymal stem cells; naturalextracts; genetically engineered living cells or otherwise modifiedliving cells; expanded or cultured cells; DNA delivered by plasmid,viral vectors, or other means; tissue transplants; autogenous tissuessuch as blood, serum, soft tissue, bone marrow; bioadhesives; bonemorphogenic proteins (BMPs); osteoinductive factor (IFO); fibronectin(FN); endothelial cell growth factor (ECGF); vascular endothelial growthfactor (VEGF); cementum attachment extracts (CAE); ketanserin; humangrowth hormone (HGH); animal growth hormones; epidermal growth factor(EGF); interleukins, for example, interleukin-1 (IL-1), interleukin-2(IL-2); human alpha thrombin; transforming growth factor (TGF-β);insulin-like growth factors (IGF-1, IGF-2); parathyroid hormone (PTH);platelet derived growth factors (PDGF); fibroblast growth factors (FGF,BFGF); periodontal ligament chemotactic factor (PDLGF); enamel matrixproteins; growth and differentiation factors (GDF); hedgehog family ofproteins; protein receptor molecules; small peptides derived from growthfactors above; bone promoters; cytokines; somatotropin; bone digesters;antitumor agents; cellular attractants and attachment agents;immuno-suppressants; permeation enhancers, for example, fatty acidesters such as laureate, myristate and stearate monoesters ofpolyethylene glycol, enamine derivatives, alpha-keto aldehydes; andnucleic acids or combinations thereof.

In certain embodiments, the bioactive agent may be a drug. In someembodiments, the bioactive agent may be a growth factor, cytokine,extracellular matrix molecule, or a fragment or derivative thereof, forexample, a protein or peptide sequence such as RGD.

In one embodiment of an implant device comprising at least one cavity,it may be contemplated that any combination or mixture of same ordifferent substances may be placed and retained therein, and further,different substances may be placed within the same or differentcavities.

Sterilization

A medical implant device according to the present disclosure includingits contents may be sterilizable. In various embodiments, one or morecomponents of the implant device and/or its contents are sterilized byradiation in a terminal sterilization step in the final packaging.Terminal sterilization of a product provides greater assurance ofsterility than from processes such as an aseptic process, which requireindividual product components to be sterilized separately and the finalpackage assembled in a sterile environment.

In various embodiments, gamma radiation is used in the terminalsterilization step, which involves utilizing ionizing energy from gammarays that penetrates deeply in the device. Gamma rays are highlyeffective in killing microorganisms, they leave no residues nor havesufficient energy to impart radioactivity to the device. Gamma rays canbe employed when the device is in the package and gamma sterilizationdoes not require high pressures or vacuum conditions, thus, packageseals and other components are not stressed. In addition, gammaradiation eliminates the need for permeable packaging materials.

In various embodiments, electron beam (e-beam) radiation may be used tosterilize one or more components of the device. E-beam radiationcomprises a form of ionizing energy, which is generally characterized bylow penetration and high-dose rates. E-beam irradiation is similar togamma processing in that it alters various chemical and molecular bondson contact, including the reproductive cells of microorganisms. Beamsproduced for e-beam sterilization are concentrated, highly-chargedstreams of electrons generated by the acceleration and conversion ofelectricity. E-beam sterilization may be used, for example, when themedical device has gel components.

Other methods may also be used to sterilize the device and/or one ormore components of the device and/or contents, including, but notlimited to, gas sterilization, such as, for example, with ethylene oxideor steam sterilization.

Method of Use

An implant device according to the present disclosure delivers thesubstance or substances in vivo. Active delivery of the substance mayinclude the cleavage of physical and/or chemical interactions ofsubstance from covering with the presence of body fluids, extracellularmatrix molecules, enzymes or cells. Further, it may comprise formationchange of substances (growth factors, proteins, polypeptides) by bodyfluids, extracellular matrix molecules, enzymes or cells.

The body of the implant device is loaded with the substance forplacement in vivo. The body may be pre-loaded, thus loaded atmanufacture, or may be loaded in the operating room or at the surgicalsite. Preloading may be done with any of the substances previouslydiscussed including, for example, allograft such as DBM, syntheticcalcium phosphates, synthetic calcium sulfates, enhanced DBM, collagen,carrier for stem cells, and expanded cells (stem cells or transgeniccells). Loading in the operating room or at the surgical site may bedone with any of these materials and further with autograft and/or bonemarrow aspirate.

Any suitable method may be used for loading a substance in the implantdevice in the operating room or at the surgical site. For example, thesubstance may be spooned into the cavity(ies) of the implant device, thesubstance may be placed in the implant device using forceps, thesubstance may be loaded into the implant device using a syringe (with orwithout a needle), or the substance may be inserted into the implantdevice in any other suitable manner. Specific embodiments for loading atthe surgical site include for example, vertebroplasty or interbody spacefiller.

For placement, the substance or substances may be provided in theimplant device and the implant device placed in vivo. In one embodiment,the implant device is placed in vivo by placing the implant device in acatheter or tubular inserter and delivering the implant device with thecatheter or tubular inserter. The implant device, with a substanceprovided therein, may be steerable such that it can be used withflexible introducer instruments for, for example, minimally invasivespinal procedures. For example, the implant device may be introduceddown a tubular retractor or scope, during XLIF, TLIF, or otherprocedures. In other embodiments, the implant device (with or withoutsubstance loaded) may be placed in a cage, for example, for interbodyfusion. Attachment mechanisms provided on the implant device may be usedto couple the device to a site in vivo.

Applications

An implant device according to the present disclosure may be configuredfor use in any suitable application. In some embodiments, the implantdevice may be used in healing vertebral compression fractures, interbodyfusion, minimally invasive procedures, posterolateral fusion, correctionof adult or pediatric scoliosis, treating long bone defects,osteochondral defects, ridge augmentation (dental/craniomaxillofacial,for example edentulous patients), beneath trauma plates, tibial plateaudefects, filling bone cysts, wound healing, around trauma, contouring(cosmetic/plastic/reconstructive surgery), and others. The implantdevice may be used in a minimally invasive procedure via placementthrough a small incision, via delivery through a tube, or other. Thesize and shape of the device may advantageously be designed inaccordance with restrictions on delivery conditions.

An exemplary application for using an implant device as disclosed isfusion of the spine. In clinical use, the implant device and deliveredsubstance may be used to bridge the gap between the transverse processesof adjacent or sequential vertebral bodies. The implant device may beused to bridge two or more spinal motion segments. The implant devicesurrounds the substance to be implanted, and contains the substance toprovide a focus for healing activity in the body. In other applications,the implant device may be applied to transverse processes or spinousprocesses of vertebrae.

Generally, the implant device may be applied to a pre-existing defect,to a created channel, or to a modified defect. Thus, for example, achannel may be formed in a bone, or a pre-existing defect may be cut toform a channel, for receipt of the implant device. The implant devicemay be configured to match the channel or defect. In some embodiments,the configuration of the implant device may be chosen to match thechannel. In other embodiments, the channel may be created, or the defectexpanded or altered, to reflect a configuration of the implant device.The implant device may be placed in the defect or channel and,optionally, coupled using attachment mechanisms.

At the time just prior to when the implant device is to be placed in adefect site, optional materials, for example, autograft bone marrowaspirate, autograft bone, preparations of selected autograft cells,autograft cells containing genes encoding bone promoting action, can becombined with the implant device and/or with a substance provided in theimplant device. The implant device can be implanted at the bone repairsite, if desired, using any suitable affixation means, for example,sutures, staples, bioadhesives, screws, pins, rivets, other fastenersand the like or it may be retained in place by the closing of the softtissues around it.

Although the disclosure has been described with reference to someembodiments, persons skilled in the art will recognize that changes maybe made in form and detail without departing from the spirit and scopeof the disclosure.

What is claimed is:
 1. A method of placing an expandable implant into adisc space, the method comprising: inserting a bottom piece into thedisc space, the bottom piece having superior and inferior surfaces and alongitudinal axis; holding the bottom piece stationary; inserting a toppiece of the expandable implant, the top piece having superior andinferior surfaces, and a tapered leading end, the leading tapered end ofthe top piece configured to distract open the disc space by slidablyinserting the top piece over the bottom piece, wherein the bottom piecehas a flat leading end face perpendicular to the longitudinal axis andthe superior surface of the bottom piece has a ramped portion extendingat an incline relative to the longitudinal axis and a non-ramped portionextending parallel to the longitudinal axis, the ramped portionextending only partially along the length of the superior surface to theleading end face such that the leading end face of the bottom piececomprises a greater height than an opposite end face of the bottompiece, the inferior surface of the top piece having a ramped portionsuch that the leading end of the top piece comprises a lesser heightthan an opposite end of the top piece.
 2. A method of claim 1, wherein(i) the top piece and the bottom piece comprise cortical bone and thetop piece further comprises a trailing end, the trailing end configuredto contact an insertion instrument or (ii) the bottom piece furthercomprising a trailing end configured to contact a ratcheting instrument.3. A method of claim 2, wherein the top piece and the bottom piececomprise a non-bone material including at least one cavity.
 4. A methodof claim 3, wherein a biocompatible material is provided within the atleast one cavity of the bottom piece or the top piece or both.
 5. Amethod of placing an expandable implant device of claim 2, wherein thesuperior surface of the bottom piece and the inferior surface of the toppiece comprise a mechanical feature configured to interlock the bottompiece with the top piece.